Erythropoietin (EPO), a 34 kDa glycoprotein, is essential for the survival and proliferation of erythroid progenitor cells and their differentiation into erythrocytes. Like most receptors for hematopoietic growth factors, the EPO receptor (EPO-R) is a type I transmembrane protein and member of the cytokine receptor superfamily (D'Andrea et al., Cell 57:277-285 (1989); and D'Andrea et al., Cell 58:1023-4 (1989)). This superfamily includes the receptors for granulocyte-macrophage colony stimulating factor (GM-CSF), granulocyte colony stimulatory factor (G-CSF), and the interleukins IL-2, IL-3, IL-4, IL-5, IL-6 and IL-7. Binding of the ligand induces rapid but transient tyrosine phosphorylation of a number of cellular proteins, including the receptors themselves. Tyrosine phosphorylation returns to basal levels after approximately 30 minutes (Miura et al., Mol Cell Biol 11:4895-902 (1991)). Thus, signalling through cytokine receptors is promoted by the activation of one or more protein-tyrosine kinases (PTKs) and presumably is terminated by one or more protein-tyrosine phosphatases (PTPs). However, little is known about which specific PTPs regulate these pathways.